Therapeutic human papillomavirus vaccines in head and neck cancer: A systematic review of current clinical trials.

Highlights • Therapeutic vaccines are seemingly safe with predominantly grade 1 and 2 toxicity. • Temporary results indicate a positive immune response to the vaccines. • Immunogenicity shows elevated antibody, IFN-γ and/or T-cell responses. • One study has demonstrated complete and partial tumour responses. Abstract Objectives This systematic review provides an overview of the current clinical trials investigating therapeutic vaccines for HPV+ head and neck cancer and discusses the future directions of therapeutic vaccine therapy. Materials and methods A systematic search was conducted in PubMed, EMBASE, Cochrane and clinicaltrials.gov for clinical trials involving therapeutic vaccines. We included studies initiated between 2000 and 2018 with patients diagnosed with HPV+ head and neck cancer and extracted data concerning type of vaccine therapy, adverse events, immunogenicity and clinical outcome measures (e.g. tumour response, progression-free survival and overall survival). Results We identified 11 studies (n = 376 patients) initiated between year 2005 and 2017. Four studies (n = 34) presented preliminary results in patients with incurable, recurrent loco-regional or distant metastatic disease indicating a positive immune response with 74% (n = 25/34 patients) having elevated antibody levels, IFN-γ and/or T-cell response. Five studies presented data on the vaccines' safety profile, demonstrating predominantly grade 1 and 2 toxicity. Three studies evaluated the clinical outcome – one study showed no complete or partial response, one study demonstrated stable disease as the best tumour response in 64% (n = 9/14 patients) and one study showed a 33% overall response rate: one patient with a complete response and seven patients with a partial response. Conclusions Treatment with therapeutic vaccines is a promising and seemingly safe strategy for patients with HPV+ head and neck cancer. However, there are not enough data to draw any further conclusions and clinical outcome measures and tumour responses to the vaccines are still missing. [ABSTRACT FROM AUTHOR]